The potential of the Camptotheca Acuminata, a tree native to China, as a source of cancer drugs was first noted by M. Wall and J. Hartwell in 1958. In 1966, M. Wall isolated Camptothecin from the bark of Camptotheca Acuminata. In the 1970's, a Camptothecin analog (i.e., sodium salt) was tested by the National Cancer Institute (NCI) in humans and was found to have serious toxic side effects; consequently, NCI decided to halt all clinical trials. Nonetheless, research to find other less toxic Camptothecin derivatives continued, and second-generation derivatives including 9-amino-Camptothecin, Topotecan, and Camptothecin 11 or CPT-11 are currently being evaluated in clinical trials. Smith Kline Beecham Pharmaceuticals discovered Topotecan, and Pharmacia Upjon is marketing CPT-11. Research Triangle Institute synthesized and evaluated 9-nitro-Camptothecin in 1986, and the Stehlin Foundation researched it, potential of use in humans.
Camptothecin constitutes approximately 0.4 percent of the dry weight of young leaves of the Camptotheca Acuminata tree. This level is 1.5-fold higher than that of the seeds and 2.5-fold higher than that of the bark as reported by McKnight and coworkers, Planta Medica 1994, 60, 558-560. It has also been reported by Buitelaar and coworkers, Plant Cell Tissue and Organ Culture 1992, 28, 11-18, that Camptothecin was produced in cell suspension cultures from Camptotheca Acuminata stem parts (no Camptothecin was detected in the media of the cell suspension cultures).
The extraction method published by Monroe and Wall (see FIG. 1) is complex, time-consuming, costly, uses large quantities of solvents and not efficient enough as far as yield is concerned.